Chronic Phase

Accelerated Phase

%

%
 
Hematology Parameters

Hemoglobin Decreased

 
62
72
80

Leukocytes Decreased

61

Neutrophils Decreased

81
85
71

Platelets Decreased

88

Biochemistry Parameters

Alanine aminotransferase (ALT) Increased

6

2

Bilirubin Increased
 Creatinine Increased

9
9

6
16

Glucose Increased

10

15

Uric Acid Increased

56

57

Glucose Decreased

8

6

6.2 Additional Data From Safety Population
 
The following adverse reactions were reported in patients in the SYNRIBO clinical studies of patients with chronic phase and accelerated phase CML at a frequency of 1 to less than 10%. Within each category, adverse reactions are ranked on the basis of frequency.

Cardiac Disorders: tachycardia, palpitations, acute coronary syndrome, angina pectoris, arrhythmia, bradycardia, ventricular extrasystoles.
 
Ear and Labyrinth Disorders: ear pain, ear hemorrhage, tinnitus.
 
Eye Disorders: cataract, vision blurred, conjunctival hemorrhage, dry eye, lacrimation increased, conjunctivitis, diplopia, eye pain, eyelid edema.
 
Gastrointestinal Disorders: stomatitis, mouth ulceration, abdominal distension, dyspepsia, gastroesophageal reflux disease, gingival bleeding, aphthous stomatitis, dry mouth, hemorrhoids, gastritis, gastrointestinal hemorrhage, melena, mouth hemorrhage, oral pain, anal fissure, dysphagia, gingival pain, gingivitis.

General Disorders and Administration Site Conditions: mucosal inflammation, pain, chest pain, hyperthermia, influenza-like illness, catheter site pain, general edema, malaise.
 
Immune System Disorders: hypersensitivity.
 
Injury, Poisoning and Procedural Complications: contusion, transfusion reaction.
 
Metabolism and Nutrition Disorders: decreased appetite, diabetes mellitus, gout, dehydration.
 
Musculoskeletal and Connective Tissue Disorders: bone pain, myalgia, muscular weakness, muscle spasms, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, musculoskeletal discomfort.
 
Nervous System Disorders: dizziness, cerebral hemorrhage, paresthesia, convulsion, hypoesthesia, lethargy, sciatica, burning sensation, dysgeusia, tremor.

Psychiatric Disorders: anxiety, depression, agitation, confusional state, mental status change.
 
Renal and Urinary Disorders: dysuria.
 
Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain, nasal congestion, dysphonia, productive cough, rales, rhinorrhea, hemoptysis, sinus congestion.
 
Skin and Subcutaneous Tissue Disorders: erythema, pruritus, dry skin, petechiae, hyperhidrosis, night sweats, ecchymosis, purpura, skin lesion, skin ulcer, rash erythematous, rash papular, skin exfoliation, skin hyperpigmentation.
 
Vascular Disorders: hematoma, hypertension, hot flush, hypotension.

7 DRUG INTERACTIONS
 
Based on the findings from in vitro drug interaction studies with SYNRIBO, no clinical drug interaction trials were warranted. [see Clinical Pharmacology (12.3)]

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy
 
Pregnancy